Iontophoresis is a method for administering charged drugs; application of an electrical current assists penetration of drugs into surface tissues. We have found that iontophoresis of 9-Beta-D-arabinofuranosyladenine-5'-monophosphate (Ara-AMP) to herpes simplex virus (HSV) lesions in animals has superior drug efficacy compared to topical application of Ara-A, 5-iodo-2'-deoxyuridine (IDU), and Ara-AMP, and IDU for HSV keratitis. We propose to induce HSV uveitis and stromal keratitis in rabbit eyes. These are examples of eye infections occurring beyond the corneal epithelium and that are difficult to treat. A new agent, 9-(2-hydroxyethoxymethyl) guanine (ACG) has excellent antiherpetic activity. Since we have shown that high levels of Ara-AMP can be obtained in the anterior chamber of rabbit eyes after iontophoresis, we predict the same results with ACG. We hope to establish that iontophoresis of Ara-AMP Iontophoresis of Ara-AMP was superior to topical application of Ara-AMP, Ara-A, and ACG will have a higher therapeutic index than topical or intravenous administration of Ara-AMP or ACG for HSV stromal keratitis and uveitis. We propose to test the effects of iontophoresis of Ara-AMP and ACG on corneal wound healing. We also hope to establish that iontophoresis of Ara-AMP and ACG will not alter the rate or quality of epithelial and stromal wound healing. We recently found that iontophoresis of epinephrine (Epi) to rabbit eyes previously infected with HSV results in virus shedding. We will determine the minimum iontophoretic treatment with Epi necessary to induce shedding and its effects on recovery of HSV from the trigeminal ganglion. We hope to establish that iontophoresis of Epi will be a safe and efficient method for obtaining HSV shedding "on command". This reactivation model will allow us to test the effects of iontophoresis of antivirals on HSV latency. If all of these studies are successful, the possibility exists that iontophoresis will be indicated in the application of antiviral drugs to HSV ocular infections in humans and furthermore, will have broad implications for delivery of other drugs by this method.